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The Parasite's Way of Life
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
As discussed in Chapter 2 (see Figure 2.34) histones are an especially important type of DNA-associated protein found in chromatin. The addition of methyl groups (methylation) to histone proteins is well-known as a mechanism that regulates whether associated DNA is in the heterochromatin or euchromatin form. Methyl groups are added to specific amino acid residues by a group of enzymes called methyltransferases. Histone methylation can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated and how many methyl groups are added. Methylation events that weaken chemical attractions between histones and DNA increase transcription because they enable the DNA to uncoil, allowing transcription factors and RNA polymerase to access the DNA.
Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
Methylation of DNA occurs through the activity of the target enzyme DNA methyltransferases (DNMTs). Solid circles (cytosine residues mostly are methylated) are bounded by histone-modifying enzymes, which subsequently recruit histone methyltransferases and histone deacetylases (HDACs). In addition, these enzymes are responsible for the induction of complex variable changes in the pattern of histone modification, which result in repressive chromatin structure establishment. Open circles = unmethylated cytosine residues; acH4K12 < lysine 12-H4 acetylene histone; mH3K9 = lysine 9–methylated histone H3; acH4K5 = lysine 5–acetylated histone H4 and mono, di, tri = all-methylated [2].
Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Administered by subcutaneous injection, in the UK, azacitidine is recommended by NICE for the treatment of chronic myelomonocytic leukemia, acute myeloid leukemia, and intermediate-2 and high-risk myelodysplastic syndromes in adults who are not eligible for hematopoietic stem cell transplantation. It becomes incorporated into DNA and forms stable complexes with methyltransferase enzymes leading to their inhibition. Thus, it acts as a DNA methylation inhibitor and blocks a number of essential cellular processes such as transcription by preventing the binding of regulatory proteins.
Nutrigenomics in Parkinson’s disease: diversity of modulatory actions of polyphenols on epigenetic effects induced by toxins
Published in Nutritional Neuroscience, 2023
Moara Rodrigues-Costa, Matheus Santos de Sousa Fernandes, Gabriela Carvalho Jurema-Santos, Lílian Vanessa da Penha Gonçalves, Belmira Lara da Silveira Andrade-da-Costa
Epigenetic mechanisms related to genetic or sporadic PD have been increasingly investigated.33–36 DNA methylation is one of the best-studied epigenetic mechanisms and occurs by the action of methyltransferase enzymes (DNMTs), usually resulting in gene silencing.34,37 The first investigations on epigenetic effects in PD sought to elucidate the role of DNA methylation on the α-syn protein synthesis.37,38 It was shown that the intron 1 region of the SNCA gene, which is essential for protein expression, is hypomethylated in the substantia nigra, putamen, and cerebral cortex of PD patients.39 This hypomethylated state of the SNCA gene was also observed in peripheral blood samples from PD patients, indicating that analysis of the SNCA methylation level in blood may be an important biomarker for early diagnosis of the disease.40 It has been suggested that the mechanisms behind this SNCA gene hypomethylation may be a result of a ‘kidnapping’ of cytosolic DNMT1 enzymes induced by α-syn aggregation itself.41
Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: a systematic review and meta-analysis
Published in Expert Review of Molecular Diagnostics, 2022
Mahdieh Razmi, Ayna Yazdanpanah, Shahroo Etemad-Moghadam, Mojgan Alaeddini, Sabrina Angelini, Leila Eini
Protein lysine methyltransferases (PKMTs) include a large family of enzymes that are known to “write’ mono-, di-, or tri-methylation marks on particular lysine residues of histone and non-histone substrates, resulting in either activation or repression of specific transcriptional programs and protein functions within the cell [4]. Preclinical investigations, particularly rich in the last three decades, have revealed the importance of these epigenetic modifiers in carcinogenesis and tumor development [5]. Among the various lysine methyltransferases, the SET and MYND domain-containing protein (SMYD) family represents an interesting example of a regulator of epigenetic and signaling pathways in both normal and pathologic conditions [6]. The SMYD family is comprised of five discrete proteins, SMYD1-5, contributing to various functions in embryonic development, cardiac and skeletal muscle activity, and cancer progression [7]. This group of proteins shares six similar domain structures from the N-terminal to C-terminal, of which SET and MYND are among the most prominent [8].
A 5-gene DNA methylation signature is a promising prognostic biomarker for early-stage cervical cancer
Published in Journal of Obstetrics and Gynaecology, 2022
Hongxia Chen, Hongying Li, Lei Wang, Yaxiong Li, ChunYan Yang
DNA methylation, a kind of epigenetic modification, may regulate gene expression and chromatin structure via DNA methyltransferase and demethylation enzymes (Li et al. 2017). It has been widely involved in the tumourigenesis and development of CC. For instance, HPV-mediated DNA methylation has been found in the aetiology of CC (Verlaat et al. 2018). The changes of gene expression due to DNA methylation have been widely observed in CC as well, including secreted frizzled-related proteins (SFRPs) (Lin et al. 2009), death-associated protein kinase 1 (DAPK-1), retinoic acid receptor beta (RARB), O6-methylguanine DNA methyltransferase (MGMT) (Sun et al. 2015), etc. Based on these novel findings, several gene methylation signatures could be used for risk stratification and early prognoses of CC patients. For example, Cai et al. (2020) identified a risk model that included a 10-gene methylation, which could discriminate CC patients of pathological stages I–III at different risk of mortality. Xu et al. (2019) identified four CC-specific methylation markers that were capable of distinguishing CC from normal tissues. Furthermore, Brebi et al. also revealed that the methylated changes of five genes could differentiate between CC and normal samples. Despite these remarkable findings, research on the DNA methylation signatures used for early-stage CC’s clinical prognosis was still limited.